The condition of the hemostatic system in acute severe peritonitis during remaxol therapy
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Cited by 2 publications
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Acute peritonitis (AP) is among the most frequent and severe conditions in pediatric abdominal surgery. Due to development of antibiotic resistance and increasing number of atypical infectious and inflammatory diseases (IIDs), a lot of specialists suggest combined treatments for these patients which should include not only surgical and etiotropic approaches, as well as therapy aimed at correction of functional defects of immunity. Neutrophilic granulocytes (NGs) reepresent a unique population of cells of primary anti-infectious immune response. Functional NG defects in pediatric AP play a leading role in development, prevalence, severity of peritoneal inflammation, and response to the therapy. Special role is given to functionally significant NG subsets responsible for triggering and implementation of phagocytosis and microbicidal properties of NG in purulent lesions and inflammatory process in children. There is an urgent need for development of new approaches to targeted immunomodulatory therapy in order to correct the NG dysfunction. The aim of the present study was to arrange the programs of immunomodulatory therapy after surgical treatment of immunocompromised children with various forms of acute peritonitis followed by subsequent evaluation of its clinical and immunological efficacy. The study included 12 immunocompromised children aged 5-12 years with different clinical course of acute peritonitis. The study group 1 included patients with local nonrestricted AP; study group 2 involved children with diffuse AP. The comparison groups consisted of 6 children who received standard therapy, i.e., clinical comparison groups 1 and 2, matched for sex, age and diagnosis. A control group consisted of 18 conditionally healthy children at similar age. Clinical examination included collection of the patient’s history, complaints, objective examination and clinical course assessment of the underlying disease. Immunological study included determination of receptor, phagocytic and microbicidal activity of NCs; assessment of NC subpopulations by their numbers and phenotype using flow cytometry, i.e., the cells co-expressing CD64, CD16, CD32, CD11b, with testing density of these membrane receptors by the MFI approach. Targeted immunomodulatory therapy programs were applied for treatment of children with unrestricted local and diffuse AP, taking into account clinical features of AP, as well as changes in number and phenotype of NC subpopulations, and impairment of their effector function. The standards of postsurgical treatment in the children with various forms of AP included different courses of treatment with Imunofan (Hexapeptide – arginyl-alpha-aspartyl-lysyl-valyl-tyrosyl-arginine; HP) using different schedules and duration. We have shown high clinical and immunological efficiency of these therapeutic programs. Thus, reversal of adequate NG functioning was observed, including positive rearrangements of negatively transformed functional NG subpopulations. In this respect, a positive clinical effect was noted in children with atypical AP with various clinical courses, i.e., absence of postsurgical complications, rapid regression of intoxication signs, normalization of body temperature, reduced volume of antibiotic therapy and shorter hospitalization terms.
Acute peritonitis (AP) is among the most frequent and severe conditions in pediatric abdominal surgery. Due to development of antibiotic resistance and increasing number of atypical infectious and inflammatory diseases (IIDs), a lot of specialists suggest combined treatments for these patients which should include not only surgical and etiotropic approaches, as well as therapy aimed at correction of functional defects of immunity. Neutrophilic granulocytes (NGs) reepresent a unique population of cells of primary anti-infectious immune response. Functional NG defects in pediatric AP play a leading role in development, prevalence, severity of peritoneal inflammation, and response to the therapy. Special role is given to functionally significant NG subsets responsible for triggering and implementation of phagocytosis and microbicidal properties of NG in purulent lesions and inflammatory process in children. There is an urgent need for development of new approaches to targeted immunomodulatory therapy in order to correct the NG dysfunction. The aim of the present study was to arrange the programs of immunomodulatory therapy after surgical treatment of immunocompromised children with various forms of acute peritonitis followed by subsequent evaluation of its clinical and immunological efficacy. The study included 12 immunocompromised children aged 5-12 years with different clinical course of acute peritonitis. The study group 1 included patients with local nonrestricted AP; study group 2 involved children with diffuse AP. The comparison groups consisted of 6 children who received standard therapy, i.e., clinical comparison groups 1 and 2, matched for sex, age and diagnosis. A control group consisted of 18 conditionally healthy children at similar age. Clinical examination included collection of the patient’s history, complaints, objective examination and clinical course assessment of the underlying disease. Immunological study included determination of receptor, phagocytic and microbicidal activity of NCs; assessment of NC subpopulations by their numbers and phenotype using flow cytometry, i.e., the cells co-expressing CD64, CD16, CD32, CD11b, with testing density of these membrane receptors by the MFI approach. Targeted immunomodulatory therapy programs were applied for treatment of children with unrestricted local and diffuse AP, taking into account clinical features of AP, as well as changes in number and phenotype of NC subpopulations, and impairment of their effector function. The standards of postsurgical treatment in the children with various forms of AP included different courses of treatment with Imunofan (Hexapeptide – arginyl-alpha-aspartyl-lysyl-valyl-tyrosyl-arginine; HP) using different schedules and duration. We have shown high clinical and immunological efficiency of these therapeutic programs. Thus, reversal of adequate NG functioning was observed, including positive rearrangements of negatively transformed functional NG subpopulations. In this respect, a positive clinical effect was noted in children with atypical AP with various clinical courses, i.e., absence of postsurgical complications, rapid regression of intoxication signs, normalization of body temperature, reduced volume of antibiotic therapy and shorter hospitalization terms.
Synthetic thymic hexapeptide in the correction of alterations of antibacterial immune defense and normalization of the profile of proinflammatory cytokines in immunocompromized Children with local unlimited acute peritonitis
The study of dysregulatory disorders of the immune system underlying the immunopathogenesis of severe purulent-inflammatory diseases (PIDs) is important for development of new therapeutic tactics of restoring antibacterial defense. Acute peritonitis (AP) is a severe PID of the abdominal cavity, the course of which are dependent on the treatment, cytokine balance and adequate functioning of the immunity. Objective: to evaluate the modulating effects on the immune system and the levels of proinflammatory cytokines of the synthetic thymic hexapeptide, active substance of Imunofan, included in the complex postoperative treatment (CPOT) of immunocompromised children with local AP. Clinical and immunological examination of 20 immunocompromised children aged 5–12 years with local AP was carried out before (study group 1, SG1) and after (study group 1a, SG1a) CPOT including synthetic thymic hexapeptide (Arginyl-alpha-AspartylLysyl-Valyl-Tyrosyl-Arginine, НР), alongside 20 conditionally healthy children (comparison group, SG). The content of T and B lymphocytes, natural killer cells (NK), levels of serum pro-inflammatory cytokines IL-1β, IL-6, TNFα, IL-8, IL-18, phagocytic and microbicidal activity of neutrophils (NG) were assessed. In SG1, before treatment, a decrease in the number of T lymphocytes, T helpers, CTL-lymphocytes, NK and an increase in the level of B lymphocytes was revealed. Defects in the effector functions of NG were determined: impaired bacterial antigen killing and decreased NADPH oxidase activity. It was established that in case of AP in immunocompromised children, the cytokine profile is characterized by overproduction of studied proinflammatory and neutrophil-associated cytokines. After complex treatment including immunomodulatory therapy, there was a restoration of the content of T lymphocytes, T helper cells, TCTL lymphocytes, an increase in the number of NK and decrease in the level of B lymphocytes. In addition, regression of the levels of inflammatory, including neutrophil-associated, cytokines and emergence of effector functions of NG due to restoration of NADPH oxidases activity, was noted. Thus, the restoration of immunological parameters in AP leads to earlier regression of the purulent-inflammatory process in the abdominal cavity and to the absence of postoperative complications. The clinical and immunological effects of the immunomodulatory therapy program with inclusion of the drug based on HP determines the feasibility of its use in the postoperative period in immunocompromised children with local AP.
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